Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles

Linling He, Natalia de Val, Charles D. Morris, Nemil Vora, Therese C. Thinnes, Leopold Kong, Parisa Azadnia, Devin Sok, Bin Zhou, Dennis R. Burton, Ian A Wilson, David Nemazee, Andrew B. Ward () and Jiang Zhu ()
Additional contact information
Linling He: The Scripps Research Institute
Natalia de Val: The Scripps Research Institute
Charles D. Morris: The Scripps Research Institute
Nemil Vora: The Scripps Research Institute
Therese C. Thinnes: The Scripps Research Institute
Leopold Kong: The Scripps Research Institute
Parisa Azadnia: The Scripps Research Institute
Devin Sok: The Scripps Research Institute
Bin Zhou: The Scripps Research Institute
Dennis R. Burton: The Scripps Research Institute
Ian A Wilson: The Scripps Research Institute
David Nemazee: The Scripps Research Institute
Andrew B. Ward: The Scripps Research Institute
Jiang Zhu: The Scripps Research Institute

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Structures of BG505 SOSIP.664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles. We then design nanoparticles presenting various forms of stabilized gp140 trimer based on ferritin and a large, 60-meric E2p that displays 20 spikes mimicking virus-like particles (VLPs). Particle assembly is confirmed by electron microscopy (EM), while antigenic profiles are generated using representative bNAbs and non-NAbs. Lastly, we demonstrate high-yield gp140 nanoparticle production and robust stimulation of B cells carrying cognate VRC01 receptors by gp120 and gp140 nanoparticles. Together, our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development.

Date: 2016
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DOI: 10.1038/ncomms12041

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